Methods for predicting patient response to modulation of the Co-stimulatory pathway

Abstract

The invention described herein relates to diagnostic and therapeutic methods and compositions useful for predicting the likelihood a patient will have favorable response to the administration of a pharmaceutically acceptable amount of an activator of the immune system (e.g, T-cells).

1 . A method for predicting the likelihood a patient with cancer will have a favorable response to therapy with a co-stimulatory pathway modulator, comprising the steps of:
 (i) measuring absolute lymphocyte count of patient samples collected over time subsequent, and optionally prior, to administration of said therapy; and   (ii) calculating a slope of said absolute lymphocyte count, wherein patients that have a negative slope have a lower likelihood of achieving a favorable response to said therapy.   
     
     
         2 . The method of  claim 1  wherein said cancer is a solid tumor. 
     
     
         3 . The method of  claim 2  wherein said cancer is selected from the group consisting of: melanoma, prostate cancer, lung cancer, non-small cell lung cancer, and small cell lung cancer. 
     
     
         4 . The method of  claim 1 ,  2 , or  3  wherein the co-stimulatory pathway modulator is a CTLA-4 antagonist. 
     
     
         5 . The method of  claim 4  wherein the CTLA-4 antagonist is selected from the group consisting of: ipilimumab and tremelimumab. 
     
     
         6 . A method of treating an individual suffering from cancer with a therapy with a co-stimulatory pathway modulator comprising the steps of:
 (i) measuring absolute lymphocyte count of patient samples collected over time subsequent, and optionally prior, to administration of said therapy; and   (ii) calculating a slope of said absolute lymphocyte count, wherein patients that have a negative slope may require a more aggressive dosing regimen of a therapeutically acceptable amount of said therapy, either alone or in combination with other agents to treat said cancer.   
     
     
         7 . The method of  claim 6  wherein said cancer is a solid tumor. 
     
     
         8 . The method of  claim 7  wherein said cancer is selected from the group consisting of: melanoma, prostate cancer, lung cancer, non-small cell lung cancer, and small cell lung cancer. 
     
     
         9 . The method of  claim 6 ,  7 , or  8  wherein the co-stimulatory pathway modulator is a CTLA-4 antagonist. 
     
     
         10 . The method of  claim 9  wherein the CTLA-4 antagonist is selected from the group consisting of: ipilimumab and tremelimumab. 
     
     
         11 . The method of  claim 10 , wherein a recommended dose for said co-stimulatory pathway modulator is administered at a dosage of about 0.1 to 15 mg/kg once every three weeks, and wherein said more aggressive dosing regimen is administered at a dosage greater than the recommended dose or greater than about 10 mg/kg once every three weeks. 
     
     
         12 . The method of  claim 10 , wherein said other agent is selected from the group consisting of: a tubulin stabilizing agent, a second co-stimulatory pathway modulator, a taxane, paclitaxel, an epothilone, IXEMPRA™, PROVENGE®, Bevacizumab, Dacarbazine, Paraplatin; Budesonide; an inhibitor of CD137; and steroids. 
     
     
         13 . A kit for use in determining a treatment regimen for an individual with cancer, comprising:
 (i) a means for measuring absolute lymphocyte counts over time, and   (ii) a means for calculating a slope for said absolute lymphocyte counts; and optionally instructions for use and interpretation of the kit results, wherein said treatment strategy comprises administration of a therapeutically effective amount of a co-stimulatory pathway modulator.   
     
     
         14 . The kit of  claim 13 , wherein said treatment regimen comprises administration of a therapeutically effective amount of a therapy selected from the group consisting of: ipilimumab and tremelimumab.